The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor.[8] Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5.
Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules.[9]
Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation.[10]
One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis.[11]
^Burnatowska-Hledin MA, Spielman WS, Smith WL, et al. (1995). "Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla". Am J Physiol. 268 (6): F1198–210. doi:10.1152/ajprenal.1995.268.6.F1198. PMID7611460.
^Burnatowska-Hledin M, Lazdins IB, Listenberger L, et al. (1999). "VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule". Am J Physiol. 276 (2 Pt 2): F199–209. doi:10.1152/ajprenal.1999.276.2.F199. PMID9950950.
Stankovic T, Byrd PJ, Cooper PR, et al. (1997). "Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes". Genomics. 40 (2): 267–76. doi:10.1006/geno.1996.4595. PMID9119394.
North WG, Fay MJ, Longo KA, Du J (1998). "Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide". Cancer Res. 58 (9): 1866–71. PMID9581826.
Burnatowska-Hledin M, Lazdins IB, Listenberger L, et al. (1999). "VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule". Am. J. Physiol. 276 (2 Pt 2): F199–209. doi:10.1152/ajprenal.1999.276.2.F199. PMID9950950.
Wada H, Yeh ET, Kamitani T (1999). "Identification of NEDD8-conjugation site in human cullin-2". Biochem. Biophys. Res. Commun. 257 (1): 100–5. doi:10.1006/bbrc.1999.0339. PMID10092517.
Burnatowska-Hledin M, Zeneberg A, Roulo A, et al. (2001). "Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle". Endothelium. 8 (1): 49–63. doi:10.3109/10623320109063157. PMID11409851.
Van Dort C, Zhao P, Parmelee K, et al. (2004). "VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways". Am. J. Physiol., Cell Physiol. 285 (6): C1386–96. doi:10.1152/ajpcell.00338.2002. PMID12917106.
Burnatowska-Hledin MA, Kossoris JB, Van Dort CJ, et al. (2004). "T47D breast cancer cell growth is inhibited by expression of VACM-1, a cul-5 gene". Biochem. Biophys. Res. Commun. 319 (3): 817–25. doi:10.1016/j.bbrc.2004.05.057. PMID15184056.